Evidence for 5-HT2 receptor mediation in quipazine anorexia.
Doses of d-amphetamine (3.2 mg/kg), fenfluramine (10 mg/kg) and quipazine (8 mg/kg) cause a significant reduction in food intake during a 30-min daily feeding session in food-deprived rats. Pirenperone and ritanserin, 5-HT2 receptor antagonists, significantly blocked the anorectic effect of quipazine, while d-amphetamine and fenfluramine effects were not modified. Metergoline, a non-specific blocker of 5-HT receptors, significantly blocked the anorectic effects of fenfluramine and quipazine, but not the d-amphetamine effect. Pretreatment with alpha- and beta-adrenergic receptor antagonists (prazosin, propranolol and pindolol), dopamine receptor antagonists (haloperidol and pimozide), the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine, and the opioid receptor antagonist naloxone failed to modify the anorectic effects of all three agents, with the exception that quipazine-induced anorexia was significantly reduced by pimozide. These results suggest that the quipazine anorexia is largely mediating through 5-HT2 receptors, although the effect of pimozide remains to be explained. Consistent with previous studies, the fenfluramine effect appears to be mediated through 5-HT1B receptors. Receptors involved in the anorectic effect of higher doses of d-amphetamine are still unidentified by this analysis. Further investigation is required to define the mechanisms by which quipazine and larger doses of d-amphetamine bring about a reduced appetite for food.
Shukla
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Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
MacKenzie-Taylor
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D
Rech
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RH
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants; D004435:Eating / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D011814:Quipazine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology
D001067:Appetite Depressants; D011804:Quinolines; D011985:Receptors, Serotonin; D005277:Fenfluramine; D011814:Quipazine; D000661:Amphetamine